Regulation of Protein Synthesis in Chick Oviduct

“Superinduction” is a phenomenon frequently observed in eukaryotic cells, whereby the inhibition of RNA synthesis (usually with actinomycin D) results in an increase in the concentration (activity) of a specific protein. This paper shows that actinomycin D can superinduce the major egg white proteins synthesized in chick magnum. After actinomycin D treatment, ovalbumin, conalbumin, ovomucoid, and lysozyme became an increased percentage of the total protein synthesized regardless of whether (a) the drug was administered to chicks or added to magnum explants in culture; and (b) protein synthesis was measured in viva or in culture. Whereas the rate of nonsecretory protein synthesis declined with a half-life of about 5 hours after actinomycin D treatment of magnum explants, the rates of ovalbumin and conalbumin synthesis declined with half-lives of 14 and 8 hours, respectively. Furthermore, actinomycin D increased the absolute rate of ovalbumin and conalbumin synthesis compared to untreated controls, despite a small decrease in the number of polysomes and the concentration of total ovalbumin mRNA. Polypeptide elongation normally limits the rate of protein synthesis in the estrogen-stimulated magnum. Two independent methods reveal that actinomycin D treatment increased-the rate of elongation 10 to 40%. The average polysome size, and the size of ovalbumin-synthesizing polysomes in particular, was maintained when actinomycin D was administered to estrogen-stimulated chicks indicating that there was a corresponding increase in the rate of initiation. During hormonal withdrawal, when initiation limits the rate of protein synthesis, actinomycin D treatment resulted in larger polysomes and an increased rate of elongation compared to untreated controls, suggesting that actinomycin D enhanced the rate of polypeptide initiation more than elongation. We propose a model to explain superinduction in this system which is based on (a) differential stability of mRNAs; and (b) competition of mRNAs for rate-limiting factors common to the translation of all mRNAs. Hence, after inhibiting RNA synthesis, the long lived mRNAs increase in